The serotonin receptor subtype 2c (5HT2c) is expressed in high abundance throughout the central nervous system (CNS) and has been identified as a target for the treatment of obesity, drug abuse, depression, anxiety, schizophrenia, and Parkinson's disease. A direct link between 5HT2c receptor system abnormalities and these diseases has proven difficult to establish, however, due to an inability to accurately quantify 5HT2c receptor density and function in the CNS. There exist only a few methods for probing 5HT2c receptors in vitro, none of which are capable of quantifying 5HT2c receptors in vivo. Thus, the development of techniques for visualizing 5HT2c receptors in vivo represents a key step in understanding both the normal function and pathophysiology of the serotonin system. Moreover, these techniques will accelerate the discovery of small molecule therapeutics that selectively interacts with the 5HT2c receptor. To provide an imaging tool for neuroscience research and drug discovery, we will develop radiotracers for positron emission tomography (PET) that can provide molecular-level information about the 5HT2c receptor system. We will accomplish this goal by labeling two potent and selective 5HT2c agonists, WAY-163909 and vabicaserin, with carbon-11. Based on our preliminary data, these compounds may provide a chemically specific map of 5HT2c receptors in the brain. The outcome of this research will be a new technology for imaging 5HT2c receptors in vivo that can be used in both preclinical and human research to establish relationships between 5HT2c physiology and brain diseases. PUBLIC HEALTH RELEVANCE: The serotonin 2c receptor subtype (5HT2c) is expressed in high abundance in the human brain and has been proposed as a target for the treatment of obesity, drug abuse, depression, anxiety, schizophrenia, and Parkinson's disease. However, direct links between these diseases and 5HT2c receptor abnormalities have been difficult to form due to a lack of tools for determining 5HT2c receptor concentration and activation. We propose to develop the first in vivo imaging agent for directly probing and quantifying 5HT2c receptors using positron emission tomography (PET). This will accelerate 5HT2c research and the discovery of 5HT2c therapeutics, which may be used to treat human brain diseases.